The immediate goal of this proposed research is to contribute to the basic knowledge of mechanisms that enable the closely-linked genes for hemoglobin synthesis in the mouse to be expressed sequentially and differentially between embryonic and adult life. Our initial studies will be on the control of non-alpha-chain synthesis in alpha-thalassemic mice which possess alleles for the single and diffuse hemoglobins at the Beta-chain locus. In alpha-thalassemic mice the major and minor Beta-chain polypeptides, which are governed by two closely-linked genes, are found in quite different concentrations than expected. The basis for the relative increase of approximately 50% in the quantity of the minor Beta chain will be investigated. The mouse model will be used to learn whether or not it is possible to control the ratio of the major and minor Beta chains incorporated into hemoglobin of alpha-thalassemic mice by treatment of mice with chemicals or hormones and whether treatment further disturbs the expected ratios of products from these closely-linked Beta-chain genes. The long-term goals are to do basic studies and to allow others to extend our findings in experimental animals to humans with hemoglobinopathies which might be ameliorated through the controlled synthesis of variant forms of hemoglobin.